The osteoclast is a giant multinucleated cell responsible for the resorption of bone matrix. This bone resorptive process is an essential step in the sequential process of bone growth and remodeling as well as in some disease processes. Stimulation of osteoclasts to resorb bone and inhibit osteoblasts from making bone probably involves the expression of an array of genes. The purpose of these studies is to characterize the regulation of a bone resorption-related gene using the human osteoclastoma tumor system. A clone representing a novel resorption-related gene was obtained from an osteoclastoma cDNA library by differential screening using probes generated from either the gaint cell tumor cells or cultured stromal cells from the same tumor. The nucleotide sequence for the partial 800bp cDNA fragment was determined. To obtain a full length cDNA clone this partial cDNA fragment was used as a probe for screening a second human osteoclastoma cDNA library. The new cDNA library was screened by plaque hybridization as well as by PCR-baaed high stringency screening method. Positive clones for the novel gene have been identified from the second cDNA library. The nucleotide sequence of these clones will determine whether they contain the full length cDNA. A full length cDNA clone will be used for protein production. Isolation and characterization of the promoter for this novel gene will allow for analysis of the regulation of this resorption-related gene particularly in osteoblast-osteoclast signaling. This approach will elucidate mechanisms of osteoblast and osteoclast function related to the resorption process. Keywords: Osteoclast, osteoblast, bone resorption.